Sulaiman Adam A A, Sobeai Homood M As, Aldawood Eman, Abogosh Ahmad, Alhazzani Khalid, Alotaibi Moureq R, Ahmad Saeed, Alhoshani Ali, Isab Anvarhusein A
Core Research Facilities (CRF), King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia.
Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran, 31261, Saudi Arabia.
Metallomics. 2022 Aug 9;14(8). doi: 10.1093/mtomcs/mfac054.
Three platinum(II) complexes of dicyclopentadiene (DCP) and dithiocarbamates (DTCs), namely, [Pt(η4-DCP)(Me2DTC)]PF6 (1), [Pt(η4-DCP)(Et2DTC)]PF6 (2), and [Pt(η4-DCP)(Bz2DTC)]PF6 (3) [Me2DTC = dimethyldithiocarbamate, Et2DTC = diethyldithiocarbamate, and Bz2DTC = dibenzyldithiocarbamate] were prepared and characterized by elemental analysis, IR, 1H, and 13C Nuclear Magnetic Resonance spectroscopy. The spectroscopic data indicated the coordination of both DCP and DTC ligands to platinum(II). The solution chemistry of complex 1 revealed that the complexes are stable in both dimethyl sulfoxide (DMSO) and 1:1 mixture of DMSO:H2O. In vitro cytotoxicity of the complexes relative to cisplatin was tested using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, against CHL-1 (human melanoma cancer cells), MDA-MB-231 (breast cancer cells), A549 (lung cancer cells), and B16 (murine melanoma cancer cells). The antiproliferative effect of all three prepared complexes was found to be significantly higher than cisplatin. Furthermore, flow cytometric analysis of complex 1 showed that the complex induced apoptosis, oxidative stress, mitochondrial potential depolarization and cell cycle arrest in a concentration-dependent pattern in the CHL-1 cells. Confirmation of apoptosis via gene expression analysis demonstrated down-regulation of anti-apoptotic genes and up-regulation of pro-apoptotic genes in the CHL-1 cells. Wound-healing assays also lent support to the strong cytotoxicity of the complexes. In vivo studies showed a significant reduction of tumor volume at the end of the experiment. In addition, the drug did not change the weight of the mice. In conclusion, complex 1 inhibited cell proliferation in vitro and reduced tumor growth in vivo.
制备了二环戊二烯（DCP）与二硫代氨基甲酸盐（DTC）的三种铂（II）配合物，即[Pt(η4-DCP)(Me2DTC)]PF6（1）、[Pt(η4-DCP)(Et2DTC)]PF6（2）和[Pt(η4-DCP)(Bz2DTC)]PF6（3）[Me2DTC = 二甲基二硫代氨基甲酸盐，Et2DTC = 二乙基二硫代氨基甲酸盐，Bz2DTC = 二苄基二硫代氨基甲酸盐]，并通过元素分析、红外光谱、1H和13C核磁共振光谱对其进行了表征。光谱数据表明DCP和DTC配体均与铂（II）配位。配合物1的溶液化学表明，该配合物在二甲基亚砜（DMSO）和DMSO:H2O的1:1混合物中均稳定。使用MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐] 测定法测试了这些配合物相对于顺铂的体外细胞毒性，针对CHL-1（人黑色素瘤癌细胞）、MDA-MB-231（乳腺癌细胞）、A549（肺癌细胞）和B16（小鼠黑色素瘤癌细胞）。发现所有三种制备的配合物的抗增殖作用均明显高于顺铂。此外，对配合物1的流式细胞术分析表明，该配合物在CHL-1细胞中以浓度依赖性模式诱导凋亡、氧化应激、线粒体膜电位去极化和细胞周期停滞。通过基因表达分析对凋亡的确认表明，CHL-1细胞中抗凋亡基因下调，促凋亡基因上调。伤口愈合试验也支持了这些配合物的强细胞毒性。体内研究表明，在实验结束时肿瘤体积显著减小。此外，该药物未改变小鼠体重。总之，配合物1在体外抑制细胞增殖，在体内减少肿瘤生长。
